1. Framingham and the Muddy Waters Jeffry N. Gerber, MD Denver’s Diet Doctor

2. “Those with cardiovascular disease not identified with diabetes… are simply undiagnosed” - Dr. Joseph R. Kraft

3. Dr. Joseph R. Kraft - diabetes-epidemic.com

4. FBG>100 mg/dl (5.5 mmol/l) screening 2hr OGTT>140 mg/dl (7.8 mmol/l) HbA1c Standard Methods Inferior

5. Gold standard based on RIA insulin (uIU/ml) 14,384 subjects, 5hr glucose plus insulin Defined 5 distinct patterns 3 patterns of hyperinsulinemia – Diabetes In-Situ Redefining diabetes at its earliest stage Dr. Kraft 5hr Insulin Assay

6. Image curtesy Ivor Cummins BE(Chem) CEng MIEI Pattern 1 - Euinsulinemia

7. Image curtesy Ivor Cummins BE(Chem) CEng MIEI Patterns 2,3,4 - Hyperinsulinemia

8. Image curtesy Ivor Cummins BE(Chem) CEng MIEI Patterns 5 - Insulinopenic

9. Hyperinsulinemia before Hyperglycemia Catherine Crofts M.Phil, B.Pharm, NZRegPharm, PhD Candidate Public Health. Images curtesy Ivor Cummins BE(Chem) CEng MIEI

10. Glucose vs. Insulin Data recompiled from Kraft J. R. Diabetes Epidemic & You. 2011

11. Euglycemia

12. Hyperglycemia

13. NHANES prevalence 2015: 49%-52% in the US now pre-diabetic or diabetic UCLA 2016: 55% of Californians are pre- diabetic or diabetic Kraft would predict that many more have hyperinsulinemia Predicting population risk Menke A, et al. JAMA. 2015;314(10):1021-1029. doi:10.1001/jama.2015.10029. healthpolicy.ucla.edu/publications/search/pages/detail.aspx?PubID=1472

14. Diabetes Paradox? Despite more diabetes & obesity there’s less heart disease Morbidity & mortally not to be confused with incidence and prevalence Diabetes Care March 2003 vol. 26 no. 3 905-910 doi: 10.2337/diacare.26.3.905

15. Atherosclerosis is a metabolic disease Missing pre-diabetes and diabetes also misses cardiovascular disease Dr. Kraft on CV risk

16. Gerald M. Reaven, MD Diabetes December 1988 vol. 37 no. 12 1595-1607 doi: 10.2337/diab.37.12.1595. Slide curtesy lipidsonline.org

18. Lipids, Smoking, HTN, Diabetes Guidelines, risk calculators Lowering cholesterol Diabetes risk buried Framingham Distraction

19. Hyperlipidemia requires remedy Mechanisms remains elusive Diet-heart hypothesis unproven Statins provide small benefit Lipid Lowering Therapy

20. Get with the Guidelines 2009 Towards a Paradigm Shift in Cholesterol Treatment 2015 Debunking the Lipid Hypothesis

21. Mark A. Creager et al. Circulation. 2003;108:1527-1532 Hyperinsulinemia and blood vessel damage

22. Framingham risk calculators: CV risk increased 2-3 fold (middle risk population) Diabetes alone: CV risk increased 6-8 fold Framingham vs. Diabetes Risk Circulation. 2002; 105: e132-e137 doi: 10.1161/01.CIR.0000013953.41667.09

23. Atherosclerosis is a symptom of diabetes Focus insulin excess, IR, and inflammation Many at risk are missed Diet and lifestyle, not medicine It’s the Insulin Stupid!

24. Low carb best Eliminating processed food Eating less Movement & activity Smoking cessation Proper sleep & happiness Diet and Lifestyle

25. Early level of suspicion FBG & HbA1c - are poor screening tools alone 2 hr OGTT including 1hr glucose <155 mg/dl (8.6 mmol/l) Insulin - fasting, 5hr assay, 2hr <30 uIU/ml Inflammatory markers, lipid quality, etc… Clinical assessment doi: http://dx.doi.org/10.1210/jc.2015-2573

26. Heart catheterization CIMT IVUS CT angiogram Coronary artery calcium score Cardiovascular imaging

28. CAC Score J Am Coll Cardiol Img. 2015;8(5):579-596

29. CAC Progression Arterioscler Thromb Vasc Biol. 2004;24:1272-1277

30. Diabetes is a Vascular Disease

31. Hyperinsulinism, Inflammation & Adiposity